AJP - Endocrinology and Metabolism, Vol 240, Issue 3 279-E285, Copyright © 1981 by American Physiological Society
Regulation of pyruvate kinase by 6-phosphogluconate in isolated hepatocytes
S. B. Smith and R. A. Freedland
Isolated liver parenchymal cells from rats fed a 65% sucrose diet for 14
days were incubated in the presence and absence of 10(-6) M glucagon. The
pyruvate kinase obtained from homogenates of the glucagon-treated cells
displayed and increased Ks 0.5 for phosphoenolpyruvate (P-enolpyruvate), as
well as an increased Ka 0.5 for 6-phosphogluconate (6-P-gluconate),
compared to pyruvate kinase from untreated cells. Additionally, glucagon
treatment decreased the maximal stimulation of pyruvate kinase by
6-P-gluconate by approximately two-thirds and decreased the Hill
coefficient value of pyruvate kinase for 6-P-gluconate from 1.76 to 1.56.
6-Aminonicotinamide, an inhibitor of 6-P-gluconate dehydrogenase, increased
6-P-gluconate levels in isolated liver parenchymal cells three- to
sevenfold, depending on the substrates present. The flux of P-enolpyruvate
through pyruvate kinase was increased from 18 to 40% in these preparations
and was highly correlated with the increase in 6-P-gluconate levels. The
results suggest that 6-P-gluconate could regulate pyruvate kinase activity
in the intact liver parenchymal cell. Furthermore, the activator would be
of greatest importance in the lipogenic animal.
